Regulation of Ocular Angiogenesis by microRNAs

抗VEGF治疗是目前治疗湿性年龄相关性黄斑变性的主要方法。 退行性变（AMD）。抗VEGF治疗的疗效仍然有限，部分患者失败 对治疗有反应目前没有药物可用于视网膜下纤维化相关的 AMD.因此，非常需要开发替代的或上级的方法， 目前对抗脉络膜新生血管形成（CNV）和视网膜下纤维化的抗VEGF疗法 在AMD。视网膜色素上皮（RPE）细胞的上皮-间质转化（EMT）可以 导致纤维化。然而，RPE EMT在AMD发病机制中的作用仍然存在， 未定义。microRNA是一类非编码RNA，可以调控多种生物学行为， 不同细胞类型的通路。miRNAs参与CNV、RPE EMT和纤维化 仍不清楚本项目的重点是阐明miRNAs在肿瘤细胞中的功能和作用机制。 AMD中涉及的复杂病理过程的背景，包括CNV、 RPE细胞和纤维化。AMD小鼠模型中RPE细胞的EMT的贡献将是 通过遗传谱系追踪进行检查。该提案的组织假设是， miRNA，miR-24，可以抑制CNV，RPE的EMT和纤维化，因此代表了一个新的研究领域。 是治疗AMD的一种优良的“一药多靶点”模型。此外，EMT的贡献 RPE细胞在AMD发病机制中的作用也将建立。目的一是定义函数 miR-24在眼部新生血管形成、炎症和纤维化中的作用目的二是确定 miR-24调节RPE细胞的EMT和纤维化。

Anti-VEGF therapy is the current mainstay for treating wet age-related macular degeneration (AMD). The efficacy of anti-VEGF therapy is still limited, and some patients failed to respond to the treatment. No drug is currently available for subretinal fibrosis associated with AMD. Therefore, there is a great need for developing alternative or superior approaches to the current anti-VEGF therapy to combat choroidal neovascularization (CNV) and subretinal fibrosis in AMD. Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells can lead to fibrosis. However, the contribution of RPE EMT in AMD pathogenesis remains undefined. MicroRNAs belong to a large group of noncoding RNAs which can regulate diverse pathways in different cell types. The involvement of miRNAs in CNV, RPE EMT and fibrosis remains unclear. This project focuses on elucidating the function and mechanism of miRNAs in the context of complex pathological processes involved in AMD, including CNV, EMT of the RPE cells and fibrosis. The contribution of EMT of RPE cells in AMD mouse models will be examined by genetic lineage tracing. The organizing hypothesis of the proposal is that a single miRNA, miR-24, can repress CNV, EMT of RPEs and fibrosis, therefore representing an excellent “one drug/multiple targets” model for treating AMD. In addition, the contribution of EMT of RPE cells in AMD pathogenesis will also be established. Aim I is to define the function of miR-24 in ocular neovascularization, inflammation and fibrosis. Aim II is to determine the role of miR-24-regulated EMT and fibrosis of RPE cells.